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新生儿膀胱来源的间充质干细胞改善糖尿病大鼠模型的膀胱功能障碍。

Neonatal Bladder-derived Mesenchymal Stem Cells Ameliorate Bladder Dysfunction in Diabetic Rat Models.

机构信息

Department of Urology, Health Sciences University, Antalya Training and Research Hospital, Antalya, Turkey.

Department of Urology, Ufuk University, School of Medicine, Ankara, Turkey.

出版信息

Urol J. 2020 Jun 23;17(4):413-421. doi: 10.22037/uj.v0i0.5504.

Abstract

PURPOSE

To evaluate the effect of a new mesenchymal stem cell type derived from the neonatal bladder (nMSC-B) on diabetic bladder dysfunction (DBD).

MATERIALS AND METHODS

nMSC-B were harvested from neonatal male Sprague-Dawley rat's bladder and expanded in culture. nMSC-B were transferred to Type-1 diabetic rats which were induced by a single dose 45 mg/kg Streptozocin (STZ). Stem cells were transferred via intraperitoneally (IP) (DM-IP group, n:6) and by direct injection to the detrusor (DM-D group, n:6) at 12th week following diabetes and compared with Phosphate Buffered Saline (PBS) injected diabetic rats (DM-PBS group, n:6) and age-matched PBS injected non-diabetic normal rats (NR-PBS group, n:6). All rats were evaluated histopathologically and functionally four weeks after the stem cell treatment.

RESULTS

nMSC-B showed improvement in both voiding function and bladder structure. The maximum voiding pressure (MVP) values in the DM-PBS group were lower compare to DM-IP, DM-D and NR-PBS groups (13.27 ± 0.78 vs 16.27 ± 0.61, 28.59 ± 2.09, 21.54 ± 1.00, respectively, P < .001). There was a significant improvement for MVP values in stem cell-treated groups. Immunohistochemical examination revealed decreased bladder smooth muscle (SM), increased fibrosis and desquamation in urothelia in diabetic groups compared to normal group(P < .001). We detected recovery in the stem cell groups. This recovery was more evident in DM-D group.  No statistical difference was observed in SM and fibrosis between DM-D and NR-PBS groups (P = .9).

CONCLUSION

It was shown that nMSCBs provided amelioration of DBD. We think that nMSC-B constitutes an effective treatment method in DBD.

摘要

目的

评估一种源自新生膀胱的新型间充质干细胞(nMSC-B)对糖尿病膀胱功能障碍(DBD)的作用。

材料和方法

从新生雄性 Sprague-Dawley 大鼠的膀胱中提取 nMSC-B 并在培养中扩增。nMSC-B 被转移到由单次剂量 45mg/kg 链脲佐菌素(STZ)诱导的 1 型糖尿病大鼠中。干细胞通过腹腔内(IP)(DM-IP 组,n:6)和直接注射到逼尿肌(DM-D 组,n:6)转移到糖尿病后第 12 周,并与磷酸盐缓冲盐水(PBS)注射的糖尿病大鼠(DM-PBS 组,n:6)和年龄匹配的 PBS 注射的非糖尿病正常大鼠(NR-PBS 组,n:6)进行比较。所有大鼠在干细胞治疗后四周进行组织病理学和功能评估。

结果

nMSC-B 改善了排尿功能和膀胱结构。DM-PBS 组的最大排尿压(MVP)值低于 DM-IP、DM-D 和 NR-PBS 组(分别为 13.27±0.78 与 16.27±0.61、28.59±2.09、21.54±1.00,P<0.001)。干细胞治疗组的 MVP 值有显著改善。免疫组织化学检查显示,与正常组相比,糖尿病组的膀胱平滑肌(SM)减少,尿路上皮纤维化和脱落增加(P<0.001)。我们检测到干细胞组的恢复。DM-D 组的恢复更为明显。DM-D 组和 NR-PBS 组的 SM 和纤维化无统计学差异(P=0.9)。

结论

结果表明 nMSCB 提供了对 DBD 的改善。我们认为 nMSC-B 是 DBD 的有效治疗方法。

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